US7288517B2 - Treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists - Google Patents
Treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists Download PDFInfo
- Publication number
- US7288517B2 US7288517B2 US10/133,967 US13396702A US7288517B2 US 7288517 B2 US7288517 B2 US 7288517B2 US 13396702 A US13396702 A US 13396702A US 7288517 B2 US7288517 B2 US 7288517B2
- Authority
- US
- United States
- Prior art keywords
- methyl
- treatment
- disease
- dihydro
- oxo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related, expires
Links
- 229940124041 Luteinizing hormone releasing hormone (LHRH) antagonist Drugs 0.000 title claims abstract description 17
- 206010012289 Dementia Diseases 0.000 title abstract description 6
- 230000004770 neurodegeneration Effects 0.000 title abstract description 5
- 208000015122 neurodegenerative disease Diseases 0.000 title abstract description 5
- 239000002474 gonadorelin antagonist Substances 0.000 claims abstract description 12
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 9
- 108700008462 cetrorelix Proteins 0.000 claims abstract description 7
- SBNPWPIBESPSIF-MHWMIDJBSA-N cetrorelix Chemical group C([C@@H](C(=O)N[C@H](CCCNC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 SBNPWPIBESPSIF-MHWMIDJBSA-N 0.000 claims abstract description 7
- 229960003230 cetrorelix Drugs 0.000 claims abstract description 7
- KATZUZNTRINHDT-HALMFYTRSA-N (2s)-1-[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-3-(4-chlorophenyl)propanoyl]amino]-3-pyridin-3-ylpropanoyl]amino]-3-hydroxypropanoyl]-methylamino]-3-(4-hydroxyphenyl)propanoyl]amino Chemical compound C([C@@H](C(=O)N[C@H](CCCCNC(N)=O)C(=O)N[C@@H](CCCC)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)N(C)C(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 KATZUZNTRINHDT-HALMFYTRSA-N 0.000 claims description 6
- 239000003163 gonadal steroid hormone Substances 0.000 claims description 6
- 239000000816 peptidomimetic Substances 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 4
- NOENHWMKHNSHGX-IZOOSHNJSA-N (2s)-1-[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-3-(4-chlorophenyl)propanoyl]amino]-3-pyridin-3-ylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-6-(ca Chemical compound C([C@H](C(=O)N[C@H](CCCCNC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 NOENHWMKHNSHGX-IZOOSHNJSA-N 0.000 claims description 3
- SMWNCXKOTUSXIC-UHFFFAOYSA-N 1-[7-chloro-3-(3,5-dimethylphenyl)-2-oxo-4-(2-piperidin-2-ylethoxy)-1h-quinolin-6-yl]-3-pyridin-2-ylurea Chemical compound CC1=CC(C)=CC(C=2C(NC3=CC(Cl)=C(NC(=O)NC=4N=CC=CC=4)C=C3C=2OCCC2NCCCC2)=O)=C1 SMWNCXKOTUSXIC-UHFFFAOYSA-N 0.000 claims description 3
- QGGCIYXVQZHCKK-UHFFFAOYSA-N 3-[[[2-[1-(3,5-difluorophenyl)-3-(2-methoxyphenyl)-1,3-dioxopropan-2-ylidene]-1,3-dihydrobenzimidazol-5-yl]amino]methyl]benzonitrile Chemical compound COC1=CC=CC=C1C(=O)C(C(=O)C=1C=C(F)C=C(F)C=1)=C1NC2=CC(NCC=3C=C(C=CC=3)C#N)=CC=C2N1 QGGCIYXVQZHCKK-UHFFFAOYSA-N 0.000 claims description 3
- 108010023617 abarelix Proteins 0.000 claims description 3
- AIWRTTMUVOZGPW-HSPKUQOVSA-N abarelix Chemical compound C([C@@H](C(=O)N[C@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)N(C)C(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 AIWRTTMUVOZGPW-HSPKUQOVSA-N 0.000 claims description 3
- 229960002184 abarelix Drugs 0.000 claims description 3
- 108010070670 antarelix Proteins 0.000 claims description 3
- 108010083551 iturelix Proteins 0.000 claims description 3
- QRYFGTULTGLGHU-NBERXCRTSA-N iturelix Chemical compound C([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CCCCNC(=O)C=1C=NC=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)CCCNC(=O)C1=CC=CN=C1 QRYFGTULTGLGHU-NBERXCRTSA-N 0.000 claims description 3
- NVJDXQUSXGIFBO-UHFFFAOYSA-N pentan-3-yl 2-(2,5-dimethylfuran-3-yl)-8-[(2-fluorophenyl)methyl]-3-[[methyl(2-pyridin-2-ylethyl)amino]methyl]-5-oxoimidazo[1,2-a]pyrimidine-6-carboxylate Chemical compound C12=NC(C3=C(OC(C)=C3)C)=C(CN(C)CCC=3N=CC=CC=3)N2C(=O)C(C(=O)OC(CC)CC)=CN1CC1=CC=CC=C1F NVJDXQUSXGIFBO-UHFFFAOYSA-N 0.000 claims description 3
- 229950011372 teverelix Drugs 0.000 claims description 3
- 238000000034 method Methods 0.000 claims 14
- 241000282412 Homo Species 0.000 claims 5
- 102000012673 Follicle Stimulating Hormone Human genes 0.000 description 5
- 108010079345 Follicle Stimulating Hormone Proteins 0.000 description 5
- 102000009151 Luteinizing Hormone Human genes 0.000 description 5
- 108010073521 Luteinizing Hormone Proteins 0.000 description 5
- 229940028334 follicle stimulating hormone Drugs 0.000 description 5
- 229940040129 luteinizing hormone Drugs 0.000 description 5
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 3
- RGHNJXZEOKUKBD-SQOUGZDYSA-N Gluconic acid Natural products OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 235000012208 gluconic acid Nutrition 0.000 description 3
- 239000000174 gluconic acid Substances 0.000 description 3
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 3
- 239000008176 lyophilized powder Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 108700012941 GNRH1 Proteins 0.000 description 2
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 2
- LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
- 159000000021 acetate salts Chemical class 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000002657 hormone replacement therapy Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- WTKYBFQVZPCGAO-LURJTMIESA-N (2s)-2-(pyridin-3-ylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC1=CC=CN=C1 WTKYBFQVZPCGAO-LURJTMIESA-N 0.000 description 1
- NIGWMJHCCYYCSF-UHFFFAOYSA-N Fenclonine Chemical group OC(=O)C(N)CC1=CC=C(Cl)C=C1 NIGWMJHCCYYCSF-UHFFFAOYSA-N 0.000 description 1
- 208000033830 Hot Flashes Diseases 0.000 description 1
- 206010060800 Hot flush Diseases 0.000 description 1
- XIGSAGMEBXLVJJ-YFKPBYRVSA-N L-homocitrulline Chemical compound NC(=O)NCCCC[C@H]([NH3+])C([O-])=O XIGSAGMEBXLVJJ-YFKPBYRVSA-N 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000035946 sexual desire Effects 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 230000002483 superagonistic effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/10—Peptides having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
- A61K38/09—Luteinising hormone-releasing hormone [LHRH], i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Definitions
- the present invention relates to the treatment of dementia and neurodegenerative diseases.
- Furuya, Shuichi et al. teach preventives and remedies for Alzheimer's disease containing a GnRH antagonist for preventing and treating Alzheimer's disease with little toxicity in WO 01/78780.
- the present invention relates to the treatment of dementia and neurodegenerative diseases with an effective dose of LHRH antagonists.
- This treatment would be accompanied by highly undesirable side effects such as the lowering of sex hormone levels to levels that result in chemical castration, e.g., loss or reduction of libido, sexual desire and sexual potency.
- side effects such as the lowering of sex hormone levels to levels that result in chemical castration, e.g., loss or reduction of libido, sexual desire and sexual potency.
- this treatment would also result in the typical symptoms of decreased levels of sex hormones such as hot flashes, etc. Women would additionally suffer from loss of bone minerals that would limit the usefulness of the treatment.
- the present invention relates to the treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists, wherein the antagonist is preferably cetrorelix, teverelix, antide or abarelix.
- the antagonist can also be the LHRH antagonist D-63 153 (Ac-D-Nal-D-p-Cl-Phe-D-Pal-Ser-N-Me-Tyr-D-Hci-Nle-Arg-Pro-D-Ala-NH 2 ) as described in the PCT application WO 00/55190 A1, where Nal is 2-napthylalanine, p-Cl-Phe is p-chlorophenylalanine, Pal is 3-pyridylalanine, Hci is homocitrulline and Nle is norleucine.
- LHRH antagonists can also exhibit a heterocyclic skeletal structure.
- Such peptidomimetics can be for example:
- An effective dose of the LHRH antagonist is given in a monthly dose of 10 to 100 mg and the treatment is administered for one month, two months or for several months.
- An effective dose is defined herein as a dose that is sufficiently limited as to not cause chemical castration.
- the LHRH antagonist is given in a monthly dose of 30 to 60 mg and the treatment is administered for one month, two months or for several months.
- compositions of the LHRH antagonist suitable for the therapeutic management of dementia and neurodegenerative diseases may be for example:
- Suitable excipients and dosage forms are, for example, described by K. H. Bauer, K. -H. Frömming and C. 5.3, Lehrbuch der Pharmazeutica Technologie, 6 th edition, Stuttgart 1999, pages 163-186 (excipients) and pages 227-386 (dosage forms). This publication, including the references as cited therein, are hereby incorporated by reference.
- the LHRH antagonist can be administered via subcutaneous, oral, intramuscular or inhalative routes.
- the disease as mentioned may be treated in accordance with the following example.
- a single dose of 30-60 mg per month of cetrorelix is administered by injection.
- the treatment is administered once a month.
- the treatment is continued for two months or lasts several months after the administration of the single dose.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Neurosurgery (AREA)
- Reproductive Health (AREA)
- Organic Chemistry (AREA)
- Endocrinology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10/133,967 US7288517B2 (en) | 2001-04-30 | 2002-04-27 | Treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US28743401P | 2001-04-30 | 2001-04-30 | |
| US10/133,967 US7288517B2 (en) | 2001-04-30 | 2002-04-27 | Treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| US20020177556A1 US20020177556A1 (en) | 2002-11-28 |
| US7288517B2 true US7288517B2 (en) | 2007-10-30 |
Family
ID=23102886
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US10/133,967 Expired - Fee Related US7288517B2 (en) | 2001-04-30 | 2002-04-27 | Treatment of dementia and neurodegenerative diseases with intermediate doses of LHRH antagonists |
Country Status (27)
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6828415B2 (en) * | 1993-02-19 | 2004-12-07 | Zentaris Gmbh | Oligopeptide lyophilisate, their preparation and use |
| US20020077327A1 (en) * | 1999-09-23 | 2002-06-20 | Neurocrine Biosciences, Inc. | Gonadotropin-releasing hormone receptor antagonists and methods relating thereto |
| PL360294A1 (en) | 2000-07-05 | 2004-09-06 | Yamanouchi Pharmaceutical Co.Ltd. | Propane-1,3-dione derivatives |
| DE10137174A1 (de) * | 2001-07-31 | 2003-02-13 | Zentaris Ag | Verwendung von LHRH-Antagonisten in nichtkastrierenden Dosen zur Verbesserung der T-Zellen-vermittelten Immunität |
| US7709519B2 (en) * | 2004-06-04 | 2010-05-04 | Astellas Pharma Inc. | Benzimidazolylidene propane-1,3 dione derivative or salt thereof |
| US20080171736A1 (en) * | 2004-12-23 | 2008-07-17 | Gregory Christopher W | Treatment of Alzheimer's Disease and Mild Cognitive impairment using GnRH-I analogs and one or more of acetylcholinesterase inhibitors and NMDA receptor antagonists |
| EP1827468B1 (en) * | 2004-12-23 | 2012-08-22 | Curaxis Pharmaceutical Corporation | Acetylcholinesterase Inhibitors and leuprolide acetate for the treatment of Alzheimer's disease |
| KR101046039B1 (ko) * | 2005-03-31 | 2011-07-01 | 아스텔라스세이야쿠 가부시키가이샤 | 프로판-1,3-디온 유도체 또는 그의 염 |
| MX2009004140A (es) * | 2006-10-21 | 2009-07-10 | Abbott Gmbh & Co Kg | Compuestos heterociclicos y su uso como inhibidores de la glucogeno sintasa quinasa 3. |
| AU2008303951A1 (en) * | 2007-09-11 | 2009-04-02 | Mondobiotech Laboratories Ag | Use of the peptide Gly-Arg-Gly-Asp-Asn-Pro as a therapeutic agent |
| JP2010538994A (ja) * | 2007-09-11 | 2010-12-16 | モンドバイオテック ラボラトリーズ アクチエンゲゼルシャフト | 例えば肺炎連鎖球菌感染症を治療するためのｂｆｇｆ１−２４および任意での（ａｒｇ８）バソプレシンの使用 |
| EP2095818A1 (en) * | 2008-02-29 | 2009-09-02 | AEterna Zentaris GmbH | Use of LHRH antagonists at non-castrating doses |
| US20110129532A1 (en) * | 2008-05-29 | 2011-06-02 | Isr Immune System Regulation Ab | Method and means for treating viral disease, in particular hiv/aids |
| CA2810954A1 (en) | 2010-09-27 | 2012-04-05 | Abbott Gmbh & Co. Kg | Heterocyclic compounds and their use as glycogen synthase kinase-3 inhibitors |
| US9090592B2 (en) | 2010-12-30 | 2015-07-28 | AbbVie Deutschland GmbH & Co. KG | Heterocyclic compounds and their use as glycogen synthase kinase-3 inhibitors |
| EP3560555A1 (en) | 2018-04-26 | 2019-10-30 | LifeArc | A composition for treating one or more estrogen related diseases |
| WO2025155903A1 (en) * | 2024-01-19 | 2025-07-24 | Temple University-Of The Commonwealth System Of Higher Education | Compositions of antioxidant translation modulators for treating neurodegenerative disorders |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3135743A (en) | 1960-06-29 | 1964-06-02 | Sterling Drug Inc | Steroido[2. 3-d]isoxazoles and preparation thereof |
| WO1997044339A1 (en) | 1996-05-20 | 1997-11-27 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| WO2000055190A1 (de) | 1999-03-17 | 2000-09-21 | Zentaris Ag | Neue lhrh-antagonisten mit verbesserten löslichkeitseigenschaften |
| WO2000069859A1 (en) | 1999-05-14 | 2000-11-23 | Neurocrine Biosciences, Inc. | Imidazo- and pyrrolo[1,2-a]pyrimid-4-ones as gonadotropin-releasing hormone receptor antagonists |
| CA2309395A1 (en) | 1999-06-04 | 2000-12-04 | Richard Lloyd Bowen | Methods for preventing and treating alzheimer's disease |
| WO2001029044A1 (en) | 1999-10-15 | 2001-04-26 | Neurocrine Biosciences, Inc. | Gonadotropin-releasing hormone receptor antagonists and methods relating thereto |
| WO2001078780A1 (fr) | 2000-04-13 | 2001-10-25 | Takeda Chemical Industries, Ltd. | Agents preventifs/remedes pour la maladie d'alzheimer |
| WO2002002533A1 (fr) | 2000-07-05 | 2002-01-10 | Yamanouchi Pharmaceutical Co., Ltd. | Derives de propane-1,3-dione |
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2002
- 2002-04-27 KR KR10-2003-7014128A patent/KR20040000446A/ko not_active Ceased
- 2002-04-27 AT AT02735312T patent/ATE400287T1/de not_active IP Right Cessation
- 2002-04-27 CA CA002444876A patent/CA2444876A1/en not_active Abandoned
- 2002-04-27 DK DK02735312T patent/DK1392348T3/da active
- 2002-04-27 SK SK1451-2003A patent/SK14512003A3/sk unknown
- 2002-04-27 PL PL36231902A patent/PL362319A1/xx not_active Application Discontinuation
- 2002-04-27 RU RU2003134949/14A patent/RU2319501C2/ru not_active IP Right Cessation
- 2002-04-27 BR BR0209290-5A patent/BR0209290A/pt not_active IP Right Cessation
- 2002-04-27 IL IL15677702A patent/IL156777A0/xx unknown
- 2002-04-27 WO PCT/EP2002/004677 patent/WO2002102401A1/en active IP Right Grant
- 2002-04-27 US US10/133,967 patent/US7288517B2/en not_active Expired - Fee Related
- 2002-04-27 EP EP02735312A patent/EP1392348B1/en not_active Expired - Lifetime
- 2002-04-27 DE DE60227507T patent/DE60227507D1/de not_active Expired - Fee Related
- 2002-04-27 AU AU2002310788A patent/AU2002310788B2/en not_active Ceased
- 2002-04-27 UA UA2003109180A patent/UA80679C2/uk unknown
- 2002-04-27 PT PT02735312T patent/PT1392348E/pt unknown
- 2002-04-27 NZ NZ544417A patent/NZ544417A/en unknown
- 2002-04-27 SI SI200230730T patent/SI1392348T1/sl unknown
- 2002-04-27 CN CNB028042964A patent/CN1317030C/zh not_active Expired - Fee Related
- 2002-04-27 MX MXPA03008666A patent/MXPA03008666A/es active IP Right Grant
- 2002-04-27 JP JP2003504987A patent/JP2004529207A/ja not_active Withdrawn
- 2002-04-27 ES ES02735312T patent/ES2307760T3/es not_active Expired - Lifetime
- 2002-04-27 HU HU0400067A patent/HUP0400067A2/hu unknown
- 2002-04-27 CZ CZ20033167A patent/CZ20033167A3/cs unknown
-
2003
- 2003-07-10 ZA ZA200305326A patent/ZA200305326B/xx unknown
- 2003-09-26 NO NO20034322A patent/NO20034322L/no not_active Application Discontinuation
- 2003-11-10 BG BG108339A patent/BG108339A/bg unknown
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3135743A (en) | 1960-06-29 | 1964-06-02 | Sterling Drug Inc | Steroido[2. 3-d]isoxazoles and preparation thereof |
| WO1997044339A1 (en) | 1996-05-20 | 1997-11-27 | Merck & Co., Inc. | Antagonists of gonadotropin releasing hormone |
| WO2000055190A1 (de) | 1999-03-17 | 2000-09-21 | Zentaris Ag | Neue lhrh-antagonisten mit verbesserten löslichkeitseigenschaften |
| WO2000069859A1 (en) | 1999-05-14 | 2000-11-23 | Neurocrine Biosciences, Inc. | Imidazo- and pyrrolo[1,2-a]pyrimid-4-ones as gonadotropin-releasing hormone receptor antagonists |
| CA2309395A1 (en) | 1999-06-04 | 2000-12-04 | Richard Lloyd Bowen | Methods for preventing and treating alzheimer's disease |
| WO2001029044A1 (en) | 1999-10-15 | 2001-04-26 | Neurocrine Biosciences, Inc. | Gonadotropin-releasing hormone receptor antagonists and methods relating thereto |
| WO2001078780A1 (fr) | 2000-04-13 | 2001-10-25 | Takeda Chemical Industries, Ltd. | Agents preventifs/remedes pour la maladie d'alzheimer |
| EP1393747A1 (en) | 2000-04-13 | 2004-03-03 | Takeda Chemical Industries, Ltd. | Preventives/remedies for alzheimer's disease |
| WO2002002533A1 (fr) | 2000-07-05 | 2002-01-10 | Yamanouchi Pharmaceutical Co., Ltd. | Derives de propane-1,3-dione |
Non-Patent Citations (6)
| Title |
|---|
| Christine Sturchler-Pierrat and Bernd Sommer. "Transgenic Animals in Alzheimer's Disease Research," Reviews in the Neurosciences, 10, 15-24 (1999). |
| Eda: N. N. Yakhno, D. R. Shtulman, P. Y. Melnitchuk, E. M. Burtsev, "The diseases of Nervous System", Zhumal Nevrologil I Palkhiatril, Maditsina Moscow 1996, pp. 114-124. |
| Herausgegeben von Lothar Thomas, Labor und Diagnose, 5. Erweiterte Auflage 2000, Seite 44, 44.2.5. |
| Kiyofumi Yamada and Toshitaka Nabeshima. "Animal models of Alzheimer's disease and evaluation of anti-demenile drugs," Pharmacology & Therapeutics 88, 93-113 (2000). |
| Reissmann T, et al. Human Reproduction Update 6(4):322-331, 2000. * |
| Serono Europe Limited, Catrotide, Apr. 13, 1999. |
Also Published As
| Publication number | Publication date |
|---|---|
| ZA200305326B (en) | 2003-07-30 |
| BR0209290A (pt) | 2004-07-13 |
| EP1392348A1 (en) | 2004-03-03 |
| AU2002310788B2 (en) | 2007-04-05 |
| EP1392348B1 (en) | 2008-07-09 |
| SK14512003A3 (sk) | 2004-08-03 |
| JP2004529207A (ja) | 2004-09-24 |
| US20020177556A1 (en) | 2002-11-28 |
| ATE400287T1 (de) | 2008-07-15 |
| CZ20033167A3 (cs) | 2004-08-18 |
| PL362319A1 (en) | 2004-10-18 |
| CN1575185A (zh) | 2005-02-02 |
| BG108339A (bg) | 2004-11-30 |
| RU2003134949A (ru) | 2005-02-10 |
| DE60227507D1 (de) | 2008-08-21 |
| NZ544417A (en) | 2008-03-28 |
| UA80679C2 (en) | 2007-10-25 |
| ES2307760T3 (es) | 2008-12-01 |
| DK1392348T3 (da) | 2008-09-29 |
| CN1317030C (zh) | 2007-05-23 |
| HK1072000A1 (en) | 2005-08-12 |
| NO20034322D0 (no) | 2003-09-26 |
| MXPA03008666A (es) | 2004-10-15 |
| RU2319501C2 (ru) | 2008-03-20 |
| PT1392348E (pt) | 2008-09-09 |
| KR20040000446A (ko) | 2004-01-03 |
| CA2444876A1 (en) | 2002-12-27 |
| IL156777A0 (en) | 2004-02-08 |
| HUP0400067A2 (hu) | 2004-04-28 |
| WO2002102401A1 (en) | 2002-12-27 |
| NO20034322L (no) | 2003-09-26 |
| SI1392348T1 (sl) | 2008-12-31 |
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